Initiation of HIV therapy

In this paper, we numerically show that the dynamics of the HIV system is sensitive to both the initial condition and the system parameters. These phenomena imply that the system is chaotic and exhibits a bifurcation behavior. To control the system, we propose to initiate an HIV therapy based on both the concentration of the HIV-1 viral load and the ratio of the CD4 lymphocyte population to the CD8 lymphocyte population. If the concentration of the HIV-1 viral load is higher than a threshold, then the first type of therapy will be applied. If the concentration of the HIV-1 viral load is lower than or equal to the threshold and the ratio of the CD4 lymphocyte population to the CD8 lymphocyte population is greater than another threshold, then the second type of therapy will be applied. Otherwise, no therapy will be applied. The advantages of the proposed control strategy are that the therapy can be stopped under certain conditions, while the state variables of the overall system is asymptotically stable with fast convergent rate, the concentration of the controlled HIV-1 viral load is monotonic decreasing, as well as the positivity constraint of the system states and that of the dose concentration is guaranteed to be satisfied. Computer numerical simulation results are presented for an illustration

Safety of opioid patch initiation in Australian residential aged care

Explores opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Abstract Objective: To explore opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Design: A cross-sectional cohort study, analysing pharmacy data on individual patient supply between 1 July 2008 and 30 September 2013. Setting: Sixty residential aged care facilities in New South Wales. Participants: Residents receiving an initial opioid patch during the study period Main outcome measure: The proportion of residents who were opioid-naive in the 4 weeks prior to patch initiation was determined. In addition, the patch strength at initiation and the daily dose of transdermal patches and of additional opioids 1 month after initiation were determined. Results: An opioid patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7% buprenorphine) in the 60 residential aged care facilities. The mean age at initiation was 87 years, and 74% of the recipients were women. The proportion of recipients who were opioid-naive before patch initiation was 34% for fentanyl and 49% for buprenorphine. Most were initiated at the lowest available patch strength, and the dose was up-titrated after initiation. Around 15% of fentanyl users and 10% of buprenorphine users needed additional regular opioids after patch initiation. Conclusions: The results suggest some inappropriate initiation of opioid patches in Australian residential aged care facilities. Contrary to best practice, a third of residents initiated on fentanyl patches were opioid-naive in the 4 weeks before initiation. &nbsp

Factors associated with antiretroviral treatment initiation amongst HIV-positive individuals linked to care within a universal test and treat programme: early findings of the ANRS 12249 TasP trial in rural South Africa

Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm3) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm3) and other eligibility criteria: ≤100; 100–200; 200–350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2–71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1–98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts

Structural visualization of key steps in human transcription initiation.

Eukaryotic transcription initiation requires the assembly of general transcription factors into a pre-initiation complex that ensures the accurate loading of RNA polymerase II (Pol II) at the transcription start site. The molecular mechanism and function of this assembly have remained elusive due to lack of structural information. Here we have used an in vitro reconstituted system to study the stepwise assembly of human TBP, TFIIA, TFIIB, Pol II, TFIIF, TFIIE and TFIIH onto promoter DNA using cryo-electron microscopy. Our structural analyses provide pseudo-atomic models at various stages of transcription initiation that illuminate critical molecular interactions, including how TFIIF engages Pol II and promoter DNA to stabilize both the closed pre-initiation complex and the open-promoter complex, and to regulate start--initiation complexes, combined with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB and explain its essential role in promoter opening

Christian Initiation: Ethics and Eschatology

(Excerpt) I did not choose the three terms of my assignment: initiation , ethics and eschatology. It would take a degree of arrogance that I do not have, to select the universe for one\u27s subject in this fashion. While I did not choose them, I am fortunate in your committee having chosen them. For in fact, as it turns out, the three terms nestle beautifully together and define a field of reflection that I have found enjoyable. Baptism is initiation into the Christian church, an ethical community. And baptism is initiation into the kingdom of God, the eschatological community. And it does both these things at once, thereby setting up a dialectic. What more could any systematic theologian ask for? That baptism does doubly initiate, is, I take it, dogma. It could be argued; but on this occasion I will assume it, and go on

Determinants of timely initiation of breastfeeding among mothers in Goba Woreda, South East Ethiopia : a cross sectional study

Background: Although breastfeeding is universal in Ethiopia, ranges of regional differences in timely initiation of breastfeeding have been documented. Initiation of breastfeeding is highly bound to cultural factors that may either enhance or inhibit the optimal practices. The government of Ethiopia developed National Infant and Young Child Feeding Guideline in 2004 and behavior change communications on breast feeding have been going on since then. However, there is a little information on the practice of timely initiation of breast feeding and factors that predict these practices after the implementation of the national guideline. The objective of this study is to determine the prevalence and determinant factors of timely initiation of breastfeeding among mothers in Bale Goba District, South East Ethiopia. Methods: A community based cross sectional study was carried out from February to March 2010 using both quantitative and qualitative methods of data collection. A total of 608 mother infant pairs were selected using simple random sampling method and key informants for the in-depth interview were selected conveniently. Descriptive statistics, bivariate analysis and multivariable logistic regression analyses were employed to identify factors associated with timely initiation of breast feeding. Results: The prevalence of timely initiation of breastfeeding was 52.4%. Bivariate analysis showed that attendance of formal education, being urban resident, institutional delivery and postnatal counseling on breast feeding were significantly associated with timely initiation of breastfeeding (P < 0.05). After adjust sting for other factors on the multivariable logistic model, being in the urban area [AOR: 4.1 (95%C.I: 2.31-7.30)] and getting postnatal counseling [AOR: 2.7(1.86-3.94)] were independent predictors of timely initiation of breastfeeding. Conclusions: The practice of timely initiation of breast feeding is low as nearly half the mothers did not start breastfeeding with one hour after delivery. The results suggest that breast feeding behavior change communication especially during the post natal period is critical in promoting optimal practice in the initiation of breast feeding. Rural mothers need special attention as they are distant from various information sources

Initiation of the detonation in the gravitationally confined detonation model of Type Ia supernovae

We study the initiation of the detonation in the gravitationally confined detonation (GCD) model of Type Ia supernovae (SNe Ia). Initiation of the detonation occurs spontaneously in a region where the length scale of the temperature gradient extending from a flow (in which carbon burning is already occurring) into unburned fuel is commensurate to the range of critical length scales which have been derived from 1D simulations that resolve the initiation of a detonation. By increasing the maximum resolution in a truncated cone that encompasses this region, beginning somewhat before initiation of the detonation occurs, we successfully simulate in situ the first gradient-initiated detonation in a whole-star simulation. The detonation emerges when a compression wave overruns a pocket of fuel situated in a Kelvin-Helmholtz cusp at the leading edge of the inwardly directed jet of burning carbon. The compression wave pre-conditions the temperature in the fuel in such a way that the Zel'dovich gradient mechanism can operate and a detonation ensues. We explore the dependence of the length scale of the temperature gradient on spatial resolution and discuss the implications for the robustness of this detonation mechanism. We find that the time and the location at which initiation of the detonation occurs varies with resolution. In particular, initiation of a detonation had not yet occurred in our highest resolution simulation by the time we ended the simulation because of the computational demand it required. We suggest that the turbulent shear layer surrounding the inwardly directed jet provides the most favorable physical conditions, and therefore the most likely location, for initiation of a detonation in the GCD model.Comment: 28 pages, 12 figures, 1 table, accepted to Ap

Effectiveness of CenteringPregnancy on Breast-Feeding Initiation Among African Americans: A Systematic Review and Meta-analysis

While breastfeeding initiation rates for African American mothers are low, an innovative model of group prenatal care, CenteringPregnancy, holds promise to increase breastfeeding rates. The aim of this systematic review and meta-analysis was to examine the effects of CenteringPregnancy versus individual prenatal care on breastfeeding initiation among African American mothers. Using a systematic approach and PRISMA guidelines, 4 electronic databases were used to search the literature. English-language studies, comparing CenteringPregnancy and individual prenatal care, including African American participants, and specifying breastfeeding initiation as an outcome were screened for inclusion. Study strength and quality were assessed and 7 studies were systematically reviewed and meta-analyzed. Participation in CenteringPregnancy increased the probability of breastfeeding initiation by 53% (95% confidence interval = 29%-81%) (n = 8047). A subgroup analysis of breastfeeding initiationamong only African American participants was performed on 4 studies where data were available. Participation in CenteringPregnancy increased the probability of breastfeeding initiation by 71% (95% confidence interval = 27%-131%) (n = 1458) for African American participants. CenteringPregnancy is an effective intervention to increase breastfeeding initiation for participants, especially for African Americans. To close the racial gap in breastfeeding initiation, high-quality research providing specific outcomes for African American participants in CenteringPregnancy are needed